Evidence for the Promotion of Bone Mineralization by 1α,25-Dihydroxycholecalciferol in the Rat Unrelated to the Correction of Deficiencies in Serum Calcium and Phosphorus

Abstract

Concurrent administration of 1alpha,25-dihydroxycholecalciferol [1alpha,25-(OH)2-CC] to intact and thyroparathyroidectomized rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) prevented or reversed the EHDP-induced inhibition of bone mineralization as measured by changes in epiphyseal plate width and ash content of bone. An analog, 1alpha-droxycholecalciferol, was also effective. Recovery of bone after EHDP treatment was also significantly improved by administration of 1alpha,25-(OH)2-CC as evidenced by enhanced uptake of 45Ca by epiphyseal plates and decreased plate widths. Cholecalciferol (CC), ergocalciferol, dihydrotachysterol2, 5,6-trans-CC, 25-OH-CC, 5,6-Trans-25-OH-CC, and 1alpha24R,25-(OH)3-CC also blocked EHDP-induced epiphyseal plate widening, but required high, pharmacological dose levels. 24R,25- (OH)2-CC was inactive at doses up to 10 microgram/day. Since EHDP-treated rats are not deficient in calcium or phosphate, these data suggest that 1alpha,25-dihydroxycholecalciferol promoted bone mineralization independently of effects upon the intestinal absorption of calcium and phosphate.

Studies of the Effects of Cholecalciferol Upon the Metabolism of Rachitic Chick Growth Cartilage

“…Cholecalciferol infusion has also been re ported to increase bone formation without affecting resorption in normal dogs [14] and bone collagen synthesis was found to be in creased in chickens [15] and rats [8] during healing of rickets. The failure of the low den sity calcified phase to be converted to the higher density hydroxyapatite phase in ra chitic chick bone appears to be related to the deficiency of vitamin D rather than to the accompanying disturbances in mineral me tabolism [16], Administration of 1,25-dihydroxycholecalciferol to chickens [17] or rats [18] can at least partly correct the inhibition of mineralization induced by treatment with ethane-1 -hydroxy-1,1 -diphosphonate but 24,25-dihydroxycholecalciferol was not found to be effective [18] and treatment with both dihydroxylated metabolites has been claimed to be necessary to prevent rachitic bone lesions in chickens maintained on a vitamin D-deficient diet [19], In vitro studies with these metabolites suggest that they can influence the synthesis of structural macro molecules; 1,25-dihydroxycholecalciferol has been reported to inhibit collagen synthesis in cultures of fetal rat calvaria [20] and in creased incorporation of 3SS 04 into proteo glycan was found in cultures of rabbit growth plate cells in the presence of either 1,25-or 24,25-dihydroxycholecalciferol [21],…”

Studies on the role of vitamin D in early skeletal development, mineralization, and growth in rats

“…A deficiency of vitamin D in young growing animals results in reduced bone mineralization and diminished concentrations of calcium and phosphorus in the plasma. The failure of normal bone mineralization in vitamin D-deficient animals may largely be the result of low plasma levels of calcium and phosphorus [3][4][5], although there is some evidence that bone mineralization may be directly promoted by 1,25-dihydroxyvitamin D3 (1,25(OH)2D:0 [6][7][8].…”

Structural and Histochemial Study of the Effect of 1,25-Dihydroxyvitamin D₃ on Long-Bone Growth Center in Suckling Mice

“…The present study showed that systemic administration of l,25(OH)2D 3 to young mice retarded their growth and was followed with increased levels of iPTH con comitant with a marked elevation in serum calcium con centration. In an in vivo system 1,25(0 H)2D 3 was found also to promote bone mineralization independently of the effects upon the intestinal absorption of calcium and phosphate [21]. The enhanced mineralization of bone has been related to the increase in osteoclastic bone resorption [22|, thus in an intact young animal l,25(OH)2D 3 seems to regulate bone turnover as well as mineral homeostasis.…”